OBJECTIVE: To evaluate the safety and tolerability of PF-04494700, an oral inhibitor of receptor for advanced glycation end products, in patients with mild-to-moderate dementia of the Alzheimer type. METHODS:Patients aged 50 years and older who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria for Alzheimer disease with an Mini-Mental State Examination (MMSE) score between 12 and 26 (inclusive) were randomized to 10 weeks of double-blind treatment with either a 10 mg "low dose" of PF-04494700 (after a 6-d loading dose of 30 mg/d), a 20 mg "high dose" of PF-04494700 (after a loading dose of 60 mg/d), or placebo. Safety measures included adverse events, laboratory tests, vital signs, and 12-lead electrocardiogram. RESULTS:Twenty-seven patients received PF-04494700 30/co mg (female: 63%; mean age: 74.6 y; mean MMSE: 21.1), 28 patients received PF-04494700 60/20 mg (female: 57%; mean age: 76.6 y; mean MMSE: 21.6), and 12 patients received placebo (female: 67%; mean age: 74.1 y; mean MMSE: 19.2). A higher proportion of patients completed 10 weeks of double-blind treatment on both the "low-dose" regimen of PF-04494700 (88.9%) and the "high-dose" regimen (85.7%) than patients who were on placebo (66.7%). Discontinuation owing to adverse events and incidence of severe adverse events, respectively, were lower in the "low-dose" regimen (7.4%, 11.1%) and the "high-dose" regimen (3.6%, 10.7%) compared with placebo (25.0%, 16.7%). There were no clinically meaningful differences in vital signs, laboratory test results, or mean electrocardiogram parameters in patients treated with PF-04494700. PF-04494700 had no consistent effect on plasma levels of β-amyloid, inflammatory biomarkers, or secondary cognitive outcomes. CONCLUSIONS: Ten weeks of treatment with PF-04494700 was safe and well tolerated in patients with mild-to-moderate Alzheimer disease, indicating the feasibility of a larger long-term efficacy trial.
RCT Entities:
OBJECTIVE: To evaluate the safety and tolerability of PF-04494700, an oral inhibitor of receptor for advanced glycation end products, in patients with mild-to-moderate dementia of the Alzheimer type. METHODS:Patients aged 50 years and older who met the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria for Alzheimer disease with an Mini-Mental State Examination (MMSE) score between 12 and 26 (inclusive) were randomized to 10 weeks of double-blind treatment with either a 10 mg "low dose" of PF-04494700 (after a 6-d loading dose of 30 mg/d), a 20 mg "high dose" of PF-04494700 (after a loading dose of 60 mg/d), or placebo. Safety measures included adverse events, laboratory tests, vital signs, and 12-lead electrocardiogram. RESULTS: Twenty-seven patients received PF-04494700 30/co mg (female: 63%; mean age: 74.6 y; mean MMSE: 21.1), 28 patients received PF-04494700 60/20 mg (female: 57%; mean age: 76.6 y; mean MMSE: 21.6), and 12 patients received placebo (female: 67%; mean age: 74.1 y; mean MMSE: 19.2). A higher proportion of patients completed 10 weeks of double-blind treatment on both the "low-dose" regimen of PF-04494700 (88.9%) and the "high-dose" regimen (85.7%) than patients who were on placebo (66.7%). Discontinuation owing to adverse events and incidence of severe adverse events, respectively, were lower in the "low-dose" regimen (7.4%, 11.1%) and the "high-dose" regimen (3.6%, 10.7%) compared with placebo (25.0%, 16.7%). There were no clinically meaningful differences in vital signs, laboratory test results, or mean electrocardiogram parameters in patients treated with PF-04494700. PF-04494700 had no consistent effect on plasma levels of β-amyloid, inflammatory biomarkers, or secondary cognitive outcomes. CONCLUSIONS: Ten weeks of treatment with PF-04494700 was safe and well tolerated in patients with mild-to-moderate Alzheimer disease, indicating the feasibility of a larger long-term efficacy trial.
Authors: Craig S Atwood; Mark E Obrenovich; Tianbing Liu; Hsien Chan; George Perry; Mark A Smith; Ralph N Martins Journal: Brain Res Brain Res Rev Date: 2003-09
Authors: C J Treutiger; G E Mullins; A-S M Johansson; A Rouhiainen; H M E Rauvala; H Erlandsson-Harris; U Andersson; H Yang; K J Tracey; J Andersson; J E W Palmblad Journal: J Intern Med Date: 2003-10 Impact factor: 8.989
Authors: L G Bucciarelli; T Wendt; L Rong; E Lalla; M A Hofmann; M T Goova; A Taguchi; S F Yan; S D Yan; D M Stern; A M Schmidt Journal: Cell Mol Life Sci Date: 2002-07 Impact factor: 9.261
Authors: Christoph Röcken; Rosemarie Kientsch-Engel; Sophie Mansfeld; Barbara Stix; Kay Stubenrauch; Bernd Weigle; Frank Bühling; Mona Schwan; Wolfgang Saeger Journal: Am J Pathol Date: 2003-04 Impact factor: 4.307
Authors: Juciano Gasparotto; Carolina S Girardi; Nauana Somensi; Camila T Ribeiro; José C F Moreira; Monique Michels; Beatriz Sonai; Mariane Rocha; Amanda V Steckert; Tatiana Barichello; João Quevedo; Felipe Dal-Pizzol; Daniel P Gelain Journal: J Biol Chem Date: 2017-11-10 Impact factor: 5.157